Naturally occurring protein could slow Alzheimer's disease

April 3, 2001 - A laboratory "fishing expedition" landed a surprising catch for researchers: a cholesterol-lowering protein produced by the body that might be able to slow the progression of Alzheimer's disease.

The findings are reported in the current (March 27) issue of Biochemistry, a peer-reviewed journal of the American Chemical Society, the world's largest scientific society.

Using a protein implicated in Alzheimer's disease - amyloid precursor protein - for bait, University of Pittsburgh researchers trolled a "lake" of chemicals specifically designed to simulate the human body to see what might grab their unusual lure. A small part of amyloid precursor protein forms a chemical called beta amyloid, which becomes the most important part of the Alzheimer's disease plaques that strangle normal brain cells.

The bait eventually produced a bite, another protein called Apolipoprotein A-1.

Everyone has some quantity of Apolipoprotein A-1, or Apo-A, in their body, says Dr. Radosveta Koldamova, M.D., Ph.D., a member of the research team. It is produced in the small intestine and the liver and is known to help prevent coronary heart disease. At normal levels, the protein clears cholesterol throughout the body, including in the brain. The scientists speculate that boosting Apo-A levels may also help clear beta amyloid.

The researchers think that increasing the concentrations of Apo-A in blood might delay the dementia associated with Alzheimer's disease. Further testing is needed to confirm their hypothesis, they add. Another such protein, Apolipoprotein E, has been similarly linked with Alzheimer's and is being studied by other researchers.

"You begin to think about whether or not changing Apo-A levels in the blood could benefit Alzheimer's patients," Koldamova said.

One way to raise the levels of the protein naturally is through a good diet, according to Professor John S. Lazo, Ph.D., who led the research study. Previous findings indicate that some foods, including fruits, soybeans, coconut oil as well as some wines and teas can stimulate cells to make more Apo-A. Liver diseases or other infections can lower Apo-A levels, he said.

In previous clinical studies, Alzheimer's patients were shown to have lower than normal levels of Apo-A, leading Koldamova to suggest a direct relationship between the two.

"We think that if we can increase the concentration of Apo-A in the blood, we might be able to increase the levels of the protein in the brain," Koldamova said. "Our hypothesis is that this might help clear beta amyloid from the brain."

Further testing is needed to confirm the role of Apo-A in animals and its relation with Alzheimer's, she said. Then, new methods to boost the protein's concentrations in the blood would be needed before any human trials could begin, she continued.

Alzheimer's disease is a progressive, degenerative disease that causes a loss of brain function, primarily among elderly people. Approximately 4 million Americans currently have Alzheimer's disease and it is estimated that 14 million Americans will have the disease by the middle of the century unless a cure or prevention is found, according to the National Institute of Aging. There is no known cure for Alzheimer's disease.

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This study was funded by the U.S. Public Health Service, a division of the U.S. Department of Health and Human Services, and the Fiske Drug Discovery Fund at the University of Pittsburgh.

The online version of the research paper cited above was initially published February 27 on the journal's Web site. Journalists can arrange access to this site by sending an email to newsroom@acs.org or calling the contact person for this release.

Radosveta Koldamova, M.D., Ph.D., is a researcher in the department of pharmacology at the University of Pittsburgh School of Medicine in Pittsburgh.

John S. Lazo, Ph.D., is a professor in the department of pharmacology at the University of Pittsburgh School of Medicine in Pittsburgh.

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